Dataset Information

The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

ABSTRACT:

Background

The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS.

Materials and methods

We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC) between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed.

Results

Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients) were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57--0.15; P = 0.02). Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046) but not between FLDMDs (-0.33%/y) and placebo (P = 0.11) or between FLDMDs and SLDMDs (P = 0.49). Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001) and FLDMDs (-0.46%/y, P<0.005), but no difference was detected between FLDMDs and placebo (P = 0.12).

Conclusions

SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.

SUBMITTER: Branger P

PROVIDER: S-EPMC4794160 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

Branger Pierre P Parienti Jean-Jacques JJ Sormani Maria Pia MP Defer Gilles G

PloS one 20160316 3

<h4>Background</h4>The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS.<h4>Materials and methods</h4>We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Med ...[more]

PMID: 26983008

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Project description:ImportanceA number of officially approved disease-modifying drugs (DMD) are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of the present study was to systematically evaluate the effect of DMDs on disability progression in RRMS.MethodsWe performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs) of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs) were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates.ResultsDMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66-0.79; p<0.001), with no evidence of heterogeneity or publication bias. In subsequent subgroup analyses, neither dichotomization of DMDs as "first" and "second" line RRMS therapies [(RR = 0.72, 95% CI = 0.65-0.80) vs. (RR = 0.72, 95% = 0.57-0.91); p = 0.96] nor the route of administration (injectable or oral) [RR = 0.75 (95% CI = 0.64-0.87) vs. RR = 0.74 (95% CI = 0.66-0.83); p = 0.92] had a differential effect on the risk of disability progression. Either considerable (5-20%) or significant (>20%) rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies.ConclusionsAvailable DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as "first" or "second" line therapies. Attrition bias needs to be taken into account in the interpretation of these findings.

Project description:To test the hypothesis that T2 signals in lesions and normal-appearing tissue are sufficiently similar that signal variations represent true variations in metabolite concentration.The T2 distributions of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) at 3.0 T were mapped in the brain of 10 relapsing-remitting (RR) MS patients of 0.3-12 years disease duration with multivoxel (four sections of 80 1-cm(3) voxels) point-resolved proton spectroscopy imaging in a two-point protocol. Institutional review board approval and written informed consent were obtained; the study was Health Insurance Portability and Accountability-compliant. Mixed-model analysis of variance was performed to compare brain regions and lesion types for each metabolite; a Wilcoxon test was performed to compare observed T2 values with age-based predictions.The T2 histograms from 320 voxels in each patient were similar in peak position for mean values (+/- standard error) for NAA (250 msec +/- 9), Cr (166 msec +/- 3), and Cho (221 msec +/- 6); shape was characterized by full width at half maximum values of 174 msec +/- 11, 98 msec +/- 3, and 143 msec +/- 5, respectively. Regional T2 values in white matter (WM; 298 msec +/- 6, 162 msec +/- 1, and 222 msec +/- 4 for NAA, Cr, and Cho, respectively) were all significantly longer than in gray matter (GM; 221 msec +/- 7, 143 msec +/- 4, and 205 msec +/- 8, respectively) but not different from isointense (313 msec +/- 24, 188 msec +/- 12, and 238 msec +/- 17, respectively) or hypointense (296 msec +/- 27, 163 msec +/- 12, and 199 msec +/- 12, respectively) lesions, except for the Cho value for hypointense lesion, which was significantly lower. When compared with corresponding values in healthy contemporaries, these T2 values were shorter by 18%, 8%, and 14% in GM and by 21%, 12%, and 13% in WM for NAA, Cr, and Cho, respectively.For the purpose of metabolic quantification at 3.0 T and echo times of less than 100 msec, an average T2 value per metabolite should suffice for any brain region and lesion regardless of disease duration, age, or disability in any RR MS patient and their controls. (c) RSNA, 2010.

Dataset Information

The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

Background

Materials and methods

Results

Conclusions

Publications

The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

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